title: The effects of BuYang HuanWu Decoction and its effective components on proliferation-related factors and ERK1/2 signal transduction pathway in cultured vascular smooth muscle cells.
abstract: Buyang Huanwu Decoction (BYHWD) was a commonly used traditional Chinese medicine for the treatment and prevention of ischemic cardiovascular and cerebral disease. Previous studies had shown that BYHWD alkaloids and glycosides could inhibit intimal hyperplasia and vascular smooth muscle cell (VSMC) proliferation after injury caused by balloon catheter. The present study aims to explore the mechanisms by which cell cycle was affected by BYHWD and its components. Primary rat VSMC was treated with platelet-derived growth factor (PDGF) and cell cycle phase and extracellular-signal regulated protein kinase (ERK) transduction pathway factors were measured. PDGF-treated cells were associated with a significant increase in the number of cells in the G(2)/M phase and S phase, and in the expression of P-ERK1/2, proliferating cell nuclear antigen (PCNA), c-fos, cyclinD(1) and cyclin-dependent kinase-4, as well as a decrease in the number of cells in the G(0)/G(1) phase, and in the expression of cyclin-dependent kinase inhibitor P21 protein and mitogen-activated protein kinase phosphatase-1 (MKP-1). Treatment with plasma of rats fed seven doses of BYHWD crude extract (22.2g/kg), BYHWD alkaloids (1.66g/kg), BYHWD glycosides (14.2g/kg) or the negative control atorvastatin (20mg/kg) inhibited these changes. All drug-containing plasma had similar activity to the mitogen activated protein kinase (MAPK)/ERK antagonist PD098059 which inhibited PDGF-induced expression of P-ERK1/2 and enhanced MKP-1. These suggest that BYHWD and its components may prevent VSMC proliferation by interfering with the ERK transduction pathway.
authors.affiliation: Pathophysiology Laboratory, Hunan University of Traditional Chinese Medicine, Shaoshan Road No. 113, Changsha, Hunan, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.forename: Lu
authors.initials: L
authors.lastname: Wu
authors.forename: Chang-Qing
authors.initials: CQ
authors.lastname: Deng
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000069059:Atorvastatin; D002317:Cardiovascular Agents / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D054638:Dual Specificity Phosphatase 1 / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D006027:Glycosides / Q000494:pharmacology*; D006538:Heptanoic Acids / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000470:Alkaloids; D002317:Cardiovascular Agents; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D005419:Flavonoids; D006027:Glycosides; D006538:Heptanoic Acids; D010982:Platelet-Derived Growth Factor; D011758:Pyrroles; C460102:buyang huanwu; D000069059:Atorvastatin; D048049:Extracellular Signal-Regulated MAP Kinases; D054638:Dual Specificity Phosphatase 1; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one